While blood and tissue eosinophilia is a hallmark of most invasive helminth infections, the full role of the eosinophil in the inflammatory reaction or the protective responses to parasites is not understood. Evidence continues to accumulate showing that the eosinophil, on an evolutionary basis, has been selected for its capacity to be cytotoxic for helminth parasites and is thereby a major defense in the host's protective immune response against these organisms, although eosinophil-associated pathology is found frequently in both atopy and helminth infections. Whatever their role, however, an understanding of how eosinophil responses are regulated, recruited to sites on inflammation and activated in filarial infections and other pathological states is one specific aim of this project. A remarkable and common feature of human helminth infections is the predominant elevations of IgE and IgG4 antibodies directed to exogenous antigens. While the preferential elevation of IgE is felt to be responsible for mediating immediate hypersensitivity reactions through binding to high affinity FcER on basophils and mast cells, the parallel increase of IgG4 with that of IgE has been postulated to act as a control element for the IgE-mediated immediate hypersensitivity reaction by blocking the access of the soluble allergens to the IgE coated mast cells. Based on this observation of a preferential and parallel response by IgE and IgG4 isotypes, it might be predicted that regulation of these two isotypes may be similar and distinct from the other IgG subclasses. The purpose of this part of the project, thus, is to understand the regulation of these two isotypes.